engleski

Study of protein specificity and selectivity by computational methods

Protein interactions are central to all cellular processes, such are for example signal transduction, protein degradation, DNA transcription, immune response. The understanding of their behaviour and functioning in a system is crucial for understanding life. For this purpose the structural and dynamical information about protein complexes is valuable and could be further exploit for protein engineering or drug design purposes. Beside protein-protein complexes, such as, complex between extracellular ribonuclease barnase and its intracellular inhibitor barstar or those between the small GTP binding Ras proteins and their effectors, we are investigating the protein complexes with small molecules, e.g. ABP1 (Auxin Binding Protein 1)-auxin and BCL (Burkholderia cepacea lipase)-alcohol complexes. Small molecules by their interaction with proteins, serve as either internal (feedback mechanism) or external regulators of molecular processes. Specifically acting small molecules, substrates and inhibitors, are of special interest because of their bioavailability and potential to accurately induce biological response. Recognition between biologically important molecules is a result of balance between different molecular properties: shape, charge distribution, entropy and dynamics. In order to investigate the molecular properties and correlate the structural parameters with biological activity we use various molecular modelling methods in our research, as well as statistical and data processing approaches. Outlines of these methods and the most important results achieved for different protein complexes will be presented. ____________________________________________________ References: Luić M , Tomić S., Leščić I., Ljubović E., Šepac D., Šunjić V., Vitale Lj., Saenger W., and Kojić-Prodić B., Eur. J. Biochem. 268 (2001) 3964-3973. Tomić S., and Kojić-Prodić B., Journal of Molecular Graphics and Modelling, 21 (2002) 3 ; 241-252. Wang T., Tomić S., Gabdouline R. R., Wade C. R., Biophysical J. 87 (2004) 1618-1630. Tumir L-M., Piantanida I., Juranović I., Meić Z., Tomić S., Žinić M., Chem. Comm. 20 (2005) 2561-2563. Tomić S. and Ramek M., Quantum Journal of Molecular Catalysis B: Enzymatic, 38 (2006), 139-147.

molecular modeling; enzyme

nije evidentirano